1. Field of the Invention
This invention relates to N-(5-tetrazolyl)-4-oxo-4H-pyrimido[2,1-b]benzothiazoles and salts thereof and to their use for the control of allergic reactions.
2. Description of the Prior Art
The pyrimido[2,1-b]benzothiazole ring system was first reported by Antaki, et al., J. Chem. Soc., 551 (1951). Other examples of this ring system were reported by Gompper, et al., Chem. Ber., 95, 2871 (1962), Galasko, et al., J. S. Afr. Chem. Inst., 22, 121 (1969), Dunwell, et al., J. Chem. Soc., (C) 2094 (1971), and Alaimo, J. Hetero. Chem., 10, 769 (1973).
U.S. Pat. No. 3,538,086 teaches the use of 4-oxo-4H-pyrimido[2,1-b]benzothiazoles as antiviral agents, while Richardson, et al., J. Med. Chem., 15, 1203 (1972) tested similar compounds as antimicrobial agents.
Allergic reactions, the symptoms resulting from an antigen-antibody interaction, manifest themselves in a wide variety of ways and in different organs and tissues. Common allergic disorders, for example, are allergic rhinitis, a condition characterized by seasonal or perennial sneezing, running nose, nasal congestion, with itching and congestion of eyes; hay fever, a variety of allergic rhinitis that results from hypersensitivity to grass pollens; and bronchial asthma, one of the most disabling and debilitating of allergic reactions, a disease characterized by hyper-reactivity of the bronchi on exposure to various immunogenic or nonimmunogenic stimuli, resulting in bronchospasms with wheezing, short-lived paroxysms and widespread constriction of airway passages. The mechanical obstruction to airflow in airways is generally reversed by the use of bronchodilators, which provide symptomatic relief. In contrast, antiallergy agents prevent the release of mediators of anaphylaxis from tissue stores to preclude elicitation of bronchoconstriction by the mediators.
Recently, Cox and co-inventors, Adv. in Drug Res., 5, 115 (1970), described the pharmacology of one such agent, disodium chromoglycate [1,3-bis-(2-carboxycromon-5-yloxy)-2-hydroxypropane, Intal]. It is not a bronchodilator, but mediates its therapeutic effects by a unique mechanism of action involving inhibition of release of mediators of anaphylaxis and is administered prophylactically. It suffers from lack of oral efficacy and, for optimum results, is administered by inhalation as a solid inhalant. Further, although it is effective against anaphylaxis due to immunoglobulin E (IgE), it is effective against anaphylaxis due to immunoglobulin G (IgG) only at high doses (60-70% protection at 100 and 300 mg./kg.).
Although the aforementioned agents represent outstanding contributions toward the treatment of asthma, many of them exert the undesired side effect of cardiac stimulation.